Cytokine loops involving interferon-γ and IP-10, a cytokine chemotactic for CD4+ lymphocytes: An explanation for the epidermotropism of cutaneous T- cell lymphoma?

A. H. Sarris, T. Esgleyes-Ribot, M. Crow, H. E. Broxmeyer, N. Karasavvas, W. Pugh, D. Grossman, A. Deisseroth, M. Duvic

Research output: Contribution to journalArticle

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Abstract

Human interferon-γ (IFN-γ)-inducible protein 10 (IP-10), a C-X-C chemokine, is secreted by IFN-γ-stimulated keratinocytes and is chemotactic for CD4+ lymphocytes. We therefore investigated its role in the epidermotropism of cutaneous T-cell lymphoma (CTCL) that is known to express IFN-γ mRNA in the epidermis and is characterized by an indolent course with multiple relapses that remain confined to the skin for many years. By injecting purified recombinant (r) IP-10 we generated a polyclonal rabbit antiserum that specifically recognized and neutralized rIP-10. With immunoperoxidase staining, IP-10 expression was limited to the basal epidermal keratinocytes of normal skin. In biopsies of CTCL lesions the expression of IP-10 was markedly increased and it extended to the suprabasal keratinocytes in 17 of 18 patients, but it was detectable only faintly in the dermal or epidermal lymphoid infiltrates in 2 of these 18 patients. In 1 patient who had matching biopsies performed before and after treatment, IP- 10 was overexpressed before treatment, but was normally expressed in the posttreatment biopsy that showed resolution of the CTCL. Increased IP-10 expression was not detected in any of 4 patients with B-cell lymphoma involving the dermis. On the basis of these findings and a review of the literature, we propose that secretion of IFN-γ by the lymphoid infiltrate in CTCL induces the epidermal keratinocytes to secrete IP-10 that, in turn, is chemotactic for CTCL, accounting for its epidermotropism. This model may be used as a basis for future investigations of the pathogenesis of CTCL.

Original languageEnglish (US)
Pages (from-to)651-658
Number of pages8
JournalBlood
Volume86
Issue number2
StatePublished - Jan 1 1995

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Chemokine CXCL10
Cutaneous T-Cell Lymphoma
T-cells
Lymphocytes
Chemokines
Cytokines
Keratinocytes
Biopsy
Interferons
Proteins
Skin
CXC Chemokines
B-Cell Lymphoma
Dermis
Epidermis
Immune Sera
Cells
Staining and Labeling
Rabbits
Recurrence

ASJC Scopus subject areas

  • Biochemistry
  • Immunology
  • Hematology
  • Cell Biology

Cite this

Cytokine loops involving interferon-γ and IP-10, a cytokine chemotactic for CD4+ lymphocytes : An explanation for the epidermotropism of cutaneous T- cell lymphoma? / Sarris, A. H.; Esgleyes-Ribot, T.; Crow, M.; Broxmeyer, H. E.; Karasavvas, N.; Pugh, W.; Grossman, D.; Deisseroth, A.; Duvic, M.

In: Blood, Vol. 86, No. 2, 01.01.1995, p. 651-658.

Research output: Contribution to journalArticle

Sarris, AH, Esgleyes-Ribot, T, Crow, M, Broxmeyer, HE, Karasavvas, N, Pugh, W, Grossman, D, Deisseroth, A & Duvic, M 1995, 'Cytokine loops involving interferon-γ and IP-10, a cytokine chemotactic for CD4+ lymphocytes: An explanation for the epidermotropism of cutaneous T- cell lymphoma?', Blood, vol. 86, no. 2, pp. 651-658.
Sarris, A. H. ; Esgleyes-Ribot, T. ; Crow, M. ; Broxmeyer, H. E. ; Karasavvas, N. ; Pugh, W. ; Grossman, D. ; Deisseroth, A. ; Duvic, M. / Cytokine loops involving interferon-γ and IP-10, a cytokine chemotactic for CD4+ lymphocytes : An explanation for the epidermotropism of cutaneous T- cell lymphoma?. In: Blood. 1995 ; Vol. 86, No. 2. pp. 651-658.
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abstract = "Human interferon-γ (IFN-γ)-inducible protein 10 (IP-10), a C-X-C chemokine, is secreted by IFN-γ-stimulated keratinocytes and is chemotactic for CD4+ lymphocytes. We therefore investigated its role in the epidermotropism of cutaneous T-cell lymphoma (CTCL) that is known to express IFN-γ mRNA in the epidermis and is characterized by an indolent course with multiple relapses that remain confined to the skin for many years. By injecting purified recombinant (r) IP-10 we generated a polyclonal rabbit antiserum that specifically recognized and neutralized rIP-10. With immunoperoxidase staining, IP-10 expression was limited to the basal epidermal keratinocytes of normal skin. In biopsies of CTCL lesions the expression of IP-10 was markedly increased and it extended to the suprabasal keratinocytes in 17 of 18 patients, but it was detectable only faintly in the dermal or epidermal lymphoid infiltrates in 2 of these 18 patients. In 1 patient who had matching biopsies performed before and after treatment, IP- 10 was overexpressed before treatment, but was normally expressed in the posttreatment biopsy that showed resolution of the CTCL. Increased IP-10 expression was not detected in any of 4 patients with B-cell lymphoma involving the dermis. On the basis of these findings and a review of the literature, we propose that secretion of IFN-γ by the lymphoid infiltrate in CTCL induces the epidermal keratinocytes to secrete IP-10 that, in turn, is chemotactic for CTCL, accounting for its epidermotropism. This model may be used as a basis for future investigations of the pathogenesis of CTCL.",
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AU - Sarris, A. H.

AU - Esgleyes-Ribot, T.

AU - Crow, M.

AU - Broxmeyer, H. E.

AU - Karasavvas, N.

AU - Pugh, W.

AU - Grossman, D.

AU - Deisseroth, A.

AU - Duvic, M.

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